Open bed type fraction collectors, for example, XY type fraction collectors, have been widely used in preparative liquid chromatography instruments for their flexibility, simplicity, efficiency, wide applicability, reliability and economy. The prior art collectors can include a platform that can accommodate various sizes of containers and configurations of rack adapters to hold tubes, bottles, vessels, pass-through/funnel-type connections as well as larger size containers for fraction collections. The collector can also have electrical components for automated control either through front panel or via direct control by sophisticated software communication protocols.
The actual collection of chromatography fractions is realized through liquid plumbing connections from chromatography instruments. After the fractions are separated from the column/cartridges in the chromatography system, they are transferred via connecting tubing to an XY type collector, flowing through a robotic arm collector tip, and are collected in containers underneath the robotic arm collector tip. The type of containers can be, for example, glass tubes, bottles, vessels, and/or pass-thru adapters, which can allow the fractions to be collected in larger size containers such as carboys. During the collection process, the robotic collector arm can move along the containers based on preset methodologies by the operator to realize the separation and collection of different fractions into their corresponding containers.
The XY type collector has wide applicability and can be used in various chromatographic systems, ranging from flash chromatography (“Flash”), low to mid-level pressure chromatography (“LPLC” and “MPLC,” respectively) to high performance liquid chromatography (“HPLC”). The XY type collector can be controlled either manually, by using a preset method from the front panel or from programmed control via software for full automation of the chromatography system. XY type collectors, as their name implies, have adapter arms that can travel only in two dimensions, i.e. no Z-movement. Typically, the arm is disposed above a grid-formation of open collection vessels, for example test tubes in which the sample is collected. In the case of many chromatography setups such as “Flash,” “LPLC,” “MPLC,” and “HPLC,” there is no need for the adapter arm to move in the Z dimension because the eluent exiting the column can easily be directed to drip down into the open collection vessels under the action of gravity alone, i.e. the eluent is in liquid phase or liquid-solid phase. Thus the advantages of the XY type collector include but are not limited to ease of use, reliability, economy, and flexibility.
Supercritical Fluid Chromatography (“SFC”) is a high-pressure, high performance chromatographic tool that can be used instead of liquid chromatography systems. Typically, today's SFC systems employ compressible fluids (e.g., carbon dioxide) at conditions above its supercritical point as a mobile phase, along with modifying solvents in most cases, to perform the chromatographic separation and purification processes. In general, SFC possesses higher efficiency, higher capacity and faster process times than other chromatography systems, for example, HPLC. SFC can significantly process more crude cleanup and separation/purification in less unit of measure, with significant reduction of toxic organic solvent waste by the use of carbon dioxide. It is therefore considered a green technique with high productivity and great economic impact.
SFC uses supercritical fluids such as carbon dioxide as the main flow solvents. The supercritical CO2 is under controlled pressure while it is flowing in the SFC chromatography system. A pressure regulator, for example a back pressure regulator (“BPR”) can be used to control the pressure of the CO2 throughout the SFC system. The BPR is typically placed in the back end of the plumbing of the chromatography system. Once the fluids pass through the BPR and are transferred to collectors, the fluid is depressurized and supercritical CO2 (as well as other compressible fluids) can be converted to gaseous vapor and vented. This leaves the sample fraction in minimal liquid volume to be collected. It is, therefore, a natural phenomenon that aerosols of liquids can be generated along with this depressurization process. The generated aerosols can carry the sample of interest from the separation process. Uncontrolled aerosols generated from this depressurization process can result in sample loss and cross contamination during collection after separation and detection, among other issues and risks, because the eluent does not simply drip straight down into a single open collection vessel, i.e. the eluent is at least partially aerosolized.
Due to the depressurization process that occurs when compressible fluids are used in an SFC system, existing collection designs for SFC chromatography use well-controlled collectors. For example, the location of the collection of the sample is enclosed inside a container that can control any resulting aerosol via means of pressure and dimensional measures. Therefore, the prior art designs typically put the location of the collection of sample inside a sealed vessel so that there is physically no chance for the aerosols to be released to the atmosphere under normal process conditions. The vessel can be made of, for example, stainless steel metal that can withstand the high pressures within an SFC process, or of glass/polymeric material with reduced pressure control (e.g., venting) at a reduced over-pressure risk level. The prior art designs can require dedicated designs with significant investment in hardware and software. This can prevent wider applicability and robustness of the collection system, among other impacts.
For several reasons, XY type collectors have not been used in SFC systems. For example, XY type collectors comprise a collector arm that is disposed above the containers, which means the location of the collection cannot be encapsulated into the sealed collection vessel. In addition, the collection arm does not have vertical movement (Z-movement, relative to X-Y plane/horizontal movement) to lower its tip down into the containers to confine the aerosols. This makes the integration of SFC instruments with XY type collectors problematic by their own design, even though there are numerous significant advantages for such integration (e.g., the combination of the high productivity of an SFC system with the flexibility, simplicity, efficiency, wide applicability, reliability and economy of an XY type collector).